Hypertension is a lifelong disease, and patients with such disease need to take medicine every day of their life, according to the Study Report on Operation Surveillance and Development Prospects of the Chinese Anti-hypertension Drugs Market from 2014 to 2019 issued by the China Industrial Information Network. The development of anti-hypertension drugs has gone through decades. Diuretics were launched in the 1960s; β-receptor antagonists were launched in the 1970s; calcium channel blockers and angiotensin-converting enzyme inhibitors (ACEI) were pushed out in the 1980s; angiotensin II receptor antagonists (Chatain) with specificity were developed in the 1990s; and successively, a plurality of prescribed preparations and compound preparations were approved by the American FDA to be launched on the market, becoming the first choices of hypertension treatment.
The prescribed anti-hypertension drugs are relatively maturely developed, and according to their mechanisms, can be basically classified into the following five types.                (1) Diuretics: hydrochlorothiazide, bumetanide, indapamide, diuretic compound preparations, etc.;        (2) Calcium channel blockers: nifedipine, amlodipine, diltiazem, verapamil, etc.;        (3) β-receptor antagonists: propranolol, atenolol, metoprolol, labetalol, etc.;        (4) Angiotensin-converting enzyme inhibitors: captopril, enalapril, benazepril, lisinopril, etc.;        (5) Angiotensin II receptor antagonists: losartan, valsartan, telmisartan, olmesartan, etc.        
The anti-hypertension drugs of different mechanisms act at different target points, and have respective advantages. During hypertension treatment, the drugs applicable to a patient are selected. The majority of the patients are usually treated with a combination method after it is proved that a single drug fails to achieve the treatment effects.
Transient receptor potential vanilloid 4 (TRPV4) is a member of the TRP, and is a non-selective cation channel. The TRPV4 channel has six transmembrane α-coiled coil domains, respectively S1-S6, has a pore ring domain through which ions are adjusted to move between S5 and S6, and has a terminal N and a terminal C both located in a cell. The TRPV4 channel must form a functional homotetramer or heterotetramer to take effect in signal transduction. The terminal N of the TRPV4 channel includes at least three ankyrin binding sites. The ankyrin can interact with the TRPV4 channel, and can inhibit the receptor IP3 so as to adjust the release of Ca2+ in cells. The TRPV4 channel has very high Ca2+ permeability, is massively expressed in vascular endothelial cells, and as a Ca2+ channel, participates in the signal transduction of the endothelial cells.
Small conductance Ca2+-activated K+ channels SKca are mainly classified into three types, KCa2.1, KCa2.2 and KCa2.3, where KCa2.3 is mainly expressed and distributed in nerve cells, colloid cells, smooth vascular muscle cells and endothelial cells. KCa2.3 plays an important role in the physiological activities of the human body, in particular in the relaxation process of smooth muscles. The continuous activation of KCa2.3 results in continuous hyperpolarization of the membrane potential in the vascular endothelial cells, and the hyperpolarization signal reaches the smooth muscles nearby. Blocking or inhibiting KCa2.3 greatly increases the vascular resistance, generates peripheral arterial resistance, and enhances blood pressure.
Research shows that TRPV4 and KCa2.3S perform physical interaction with each other on the vascular endothelial cells. Ca2+ enters the cells via the TPR channels to activate the potassium ion channels and then to cause vasodilatation. However, the specific interacting site is still unknown. Searching for the interacting site and finding a compound which works at the site has great significance for the research and development of anti-hypertension drugs.